Heart failure is a debilitating disease in which abnormal function of the heart leads in the direction of inadequate blood flow to fulfill the needs of the tissues and organs of the body. Typically, the heart loses propulsive power because the cardiac muscle loses capacity to stretch and contract. Often, the ventricles do not adequately eject or fill with blood between heartbeats and the valves regulating blood flow become leaky, allowing regurgitation or back-flow of blood. The impairment of arterial circulation deprives vital organs of oxygen and nutrients. Fatigue, weakness and the inability to carry out daily tasks may result. Not all heart failure patients suffer debilitating symptoms immediately. Some may live actively for years. Yet, with few exceptions, the disease is relentlessly progressive. As heart failure progresses, it tends to become increasingly difficult to manage. Even the compensatory responses it triggers in the body may themselves eventually complicate the clinical prognosis. For example, when the heart attempts to compensate for reduced cardiac output, it adds muscle causing the ventricles (particularly the left ventricle) to grow in thickness in an attempt to pump more blood with each heartbeat. This places a still higher demand on the heart's oxygen supply. If the oxygen supply falls short of the growing demand, as it often does, further injury to the heart may result. The additional muscle mass may also stiffen the heart walls to hamper rather than assist in providing cardiac output. A particularly severe form of heart failure is congestive heart failure (CHF) wherein the weak pumping of the heart leads to build-up of fluids in the lungs and other organs and tissues.
Heart failure is often associated with electrical signal conduction defects within the heart. The natural electrical activation system through the heart involves sequential events starting with the sino-atrial (SA) node, and continuing through the atrial conduction pathways of Bachmann's bundle and internodal tracts at the atrial level, followed by the atrio-ventricular (AV) node, the Bundle of His, the right and left bundle branches, with final distribution to the distal myocardial terminals via the Purkinje fiber network. Any of these conduction pathways may potentially be degraded. A common conduction defect arising in connection with CHF is left bundle branch block (LBBB). The left bundle branch forms a broad sheet of conduction fibers along the septal endocardium of the left ventricle and separates into two or three indistinct fascicles. These extend toward the left ventricular apex and innervate both papillary muscle groups. The main bundle branches are nourished by septal perforating arteries. In a healthy heart, electrical signals are conducted more or less simultaneously through the left and right bundles to trigger synchronous contraction of both the septal and postero-lateral walls of the left ventricle. LBBB occurs when conduction of electrical signals through the left bundle branch is delayed or totally blocked, thereby delaying delivery of the electrical signal to the left ventricle and altering the sequence of activation of that ventricle. The impulse starts in the right ventricle (RV) and crosses the septum causing the interventricular septum to depolarize and hence, contract, first. The electrical impulse continues to be conducted to the postero-lateral wall of the left ventricle causing its activation and depolarization but, due to an inability to use the native conduction system, this activation and contraction is delayed. As such, the posterolateral wall of the left ventricle (LV) only starts to contract after the interventricular septum has completed its contraction and is starting to relax. LBBB thus results in an abnormal activation of the left ventricle inducing desynchronized ventricular contraction (i.e. ventricular dyssynchrony) and impairment in cardiac performance.
Degeneration of the electrical conduction system as manifested by LBBB or other conduction defects may come from an acute myocardial infarction but is usually associated with the degeneration as a result of chronic ischemia, left ventricular hypertension, general aging and calcification changes and stretch, especially any form of cardiac myopathy that results in overt CHF. Present treatments are directed towards correcting this electrical correlate by pacing on the left side of the heart and/or pacing on both sides of the left ventricle (lateral-posterior wall and septum) to improve contractile coordination. One particular technique for addressing LBBB is cardiac resynchronization therapy (CRT), which seeks to normalize asynchronous cardiac electrical activation and the resultant asynchronous contractions by delivering synchronized pacing stimulus to both sides of the ventricles using pacemakers or ICDs equipped with biventricular pacing capability, i.e. CRT seeks to reduce or eliminate ventricular dyssynchrony. Ventricular stimulus is synchronized so as to help to improve overall cardiac function. This may have the additional beneficial effect of reducing the susceptibility to life-threatening tachyarrhythmias. With CRT, pacing pulses are delivered directly to the left ventricle in an attempt to ensure that the left ventricular myocardium will contract more uniformly. CRT may also be employed for patients whose nerve conduction pathways are corrupted due to right bundle branch block (RBBB) or due to other problems such as the development of scar tissue within the myocardium following a myocardial infarction. CRT and related therapies are discussed in, for example, U.S. Pat. No. 6,643,546 to Mathis, et al., entitled “Multi-Electrode Apparatus And Method For Treatment Of Congestive Heart Failure”; U.S. Pat. No. 6,628,988 to Kramer, et al., entitled “Apparatus And Method For Reversal Of Myocardial Remodeling With Electrical Stimulation”; and U.S. Pat. No. 6,512,952 to Stahmann, et al., entitled “Method And Apparatus For Maintaining Synchronized Pacing”.
With conventional CRT, an external Doppler-echocardiography system may be used to noninvasively assess cardiac function. It can also be used to assess the effectiveness of any programming changes on overall cardiac function. Then, biventricular pacing control parameters of the pacemaker or ICD are adjusted by a physician using an external programmer in an attempt to synchronize the ventricles and to optimize patient cardiac function. For example, the physician may adjust the interventricular pacing delay, which specifies the time delay between pacing pulses delivered to the right and left ventricles, in an attempt to maximize cardiac output. To assess the effectiveness of any programming change, Doppler-echocardiography, impedance cardiography or some other independent measure of cardiac function is utilized. However, this evaluation and programming requires an office visit and is therefore a timely and expensive process. It also restricts the evaluation to a resting state, commonly with the patient in a supine position. As such, the system is not necessarily optimized for activity, for the upright position, for other times of day since there may also be a circadian rhythm to cardiac function. Also, heart rate and blood pressure have diurnal or circadian variations. Moreover, when relying on any external hemodynamic monitoring system, the control parameters of the pacemaker or ICD cannot be automatically adjusted to respond to on-going changes in patient cardiac function.
Accordingly, it is desirable to configure an implanted device to automatically and frequently evaluate the degree of ventricular dyssynchrony within a patient, particularly within those suffering from heart failure, and to automatically adjust the CRT pacing parameters to reduce the degree of dyssynchrony and improve cardiac output. Heretofore, various techniques for use by implantable devices for evaluating ventricular dyssynchrony have exploited the relative timing of left and right ventricular depolarization events within an intracardiac electrogram (IEGM) signal sensed by the device. In this regard, mechanical contraction of the ventricles is manifest within the IEGM as an electrical depolarization event referred to as the QRS-complex. The QRS-complex is usually preceded by a P-wave, which corresponds to the electrical depolarization of the atria. The QRS-complex is usually followed by a T-wave, which corresponds to the electrical repolarization of the ventricles. (The repolarization of the atria typically generates an electrical signal too weak to be reliably detected.) As already explained, ventricular dyssynchrony results from asynchronous mechanical contractions of the ventricles, i.e. the left and right ventricles do not contract at precisely the same time. As such, the electrical depolarization signals generated within the left and right ventricles are likewise asynchronous. That is, the QRS-complex of the left ventricle is no longer synchronized with that of the right ventricle. Accordingly, ventricular dyssynchrony can be detected by separately detecting the depolarization of the LV and the depolarization of the RV, i.e. by separately detect both an LV QRS-complex and an RV QRS-complex. Any significant time delay therebetween is indicative of ventricular dyssynchrony. CRT is then performed in an effort to reduce that dyssynchrony, i.e. pacing pulses are separately applied to the left and right ventricles subject to an interventricular pacing delay set by the device in an attempt to re-synchronize the ventricles.
Techniques for detecting ventricular dyssynchrony based on QRS-complexes and for delivering CRT in response thereto are set forth in some of the above-cited patents. However, problems remain. One particular problem with QRS-complex-based techniques is that they are optimal only if the ventricles contract due to intrinsic electrical stimulation (i.e. the stimulation reaches the ventricles along the aforementioned natural AV conduction pathways.) If the ventricles are being paced by the implanted device, then the QRS-complex morphology within the IEGM can change greatly affecting the performance of the QRS-complex-based technique. Rather, an evoked response (ER) appears within the IEGM, which is representative of the depolarization of the ventricular myocardium due to the application of an artificial pacing pulse. The shape of the ER typically differs from that of the QRS-complex. Moreover, time delays between ERs cannot typically be used to detect ventricular dyssynchrony since the ERs are themselves synchronized with the pacing pulses, which are artificially applied. This presents a significant problem during CRT, since ventricular pacing pulses are preferably delivered for each heartbeat. Hence, during CRT, it would not be optimal to use QRS-complex-based dyssynchrony detection techniques to evaluate the degree of ventricular dyssynchrony to, e.g., verify that CRT is effective or to adjust the interventricular pacing delay. It is possible to temporarily suspend CRT in order to allow the ventricles to beat naturally so that the degree of dyssynchrony can again be evaluated via an analysis of the QRS-complexes. However, this technique, in addition to being undesired clinically, does not necessarily provide an indication of the amount of dyssynchrony, if any, occurring during actual delivery of CRT pacing.
Accordingly, it is desirable to provide techniques for detecting ventricular dyssynchrony that do not necessarily require detection of QRS-complexes and it is to this end that the invention is generally directed.
Heretofore, at least some techniques have been developed for controlling CRT or for evaluating ventricular dyssynchrony that do not rely on interventricular delays measured from QRS-complexes. See, for example, U.S. patent application Ser. No. 11/558,194, of Panescu et al., filed Nov. 9, 2006, entitled “Closed-Loop Adaptive Adjustment of Pacing Therapy based on Cardiogenic Impedance Signals Detected by an Implantable Medical Device,” which sets forth techniques wherein mechanical interventricular conduction delays are elevated based on a cardiogenic impedance signal. See also, U.S. patent application Ser. No. 11/557,887, of Shelchuk, filed Nov. 8, 2006, entitled “Systems and Methods for Evaluating Ventricular Dyssynchrony Using Atrial and Ventricular Pressure Measurements Obtained by an Implantable Medical Device,” which sets forth techniques wherein mechanical interventricular conduction delays are elevated based on atrial and ventricular pressure measurements. See, also, U.S. Pat. No. 7,072,715 to Bradley, entitled “Implantable Cardiac Stimulation Device for and Method of Monitoring Progression or Regression of Heart Disease by Monitoring Evoked Response Features,” which exploits certain features of the ER to detect progression or regression of heart disease, though it does not specifically evaluate the degree of ventricular dyssynchrony.
Herein, additional and alternative techniques are provided for evaluating ventricular dyssynchrony and for controlling CRT or other forms of stimulation therapy that do not rely on QRS-complexes.